Bilirubin, a catabolic product of red cells and hemoproteins, is normally detoxified by the liver. This bile pigment is extremely toxic to some tissues, and so it is bound to serum albumin to prevent its entry into body cells during its transport to the liver. However, the newborn infant has multiple defects in the formation and excretion of bilirubin, as well as having a relatively low serum albumin. Consequently in the newborn, serum bilirubin levels can rise to the point where serum albumin becomes saturated, and bilirubin spills into the tissues. The brain is especially vulnerable to the deleterious effects, some of which include inhibition of tissue respiration, loss of the ability to form energy, and loss of the integrity of cell membranes. This project is designed to determine the following: (1) how does bilirubin kill cells, (2) what factors govern the binding of bilirubin to albumin, (3) what factors govern the uptake of bilirubin by tissues, and (4) why are some tissues more vulnerable to the poisonous effects of bilirubin than others? It is hoped that the information can be applied to the hyperbilirubinemic newborn so that no infant will suffer brain damage from this bile pigment. A variety of subcellular organelles, cells, tissues, and whole animals will be used to measure the metabolic functions altered by bilirubin. Spectrophotometric, ORD-CD, enzymic and other biochemical and metabolic methods will be employed to study the nature of the bilirubin-albumin bond under a number of altered situations such as pH, presence of absence of lipid, ionic strength and other parameters simulating physiological and clinical conditions.